Analysis of protocadherin alpha gene deletion variant in bipolar disorder and schizophrenia

Objectives The cell adhesion proteins protocadherins and cadherins, through their effects on guiding neurons during development, neuronal differentiation, and synaptogenesis, are feasible targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Thus, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider as underlying susceptibility factors. One such set of candidate genes is the 5q31-linked PCDH family. A polymorphic copy number variation in this locus, a 16.7-kb deletion affecting PCDH-α exons 8-10 (α8- α10δ), was analyzed in this study as a potential candidate variant in SZ and BD. Methods The frequency of the α8-α10δ variant was determined in a cohort of Caucasian patients with SZ from the United States and a cohort of patients with BD from the Czech Republic, and corresponding controls by amplifying DNA with deletion specific primers followed by gel electrophoresis. Results No significant difference was observed in the frequency of the α8-α10δ variant in patients with SZ or BD compared with their respective controls. Conclusion Although the results of this study were negative, theoretical considerations and linkage studies suggest that the 5q31-linked PCDH family should be analyzed as a potential locus underlying SZ and BD susceptibility. Psychiatr Genet 18:110-115